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41.
Tumor Necrosis Factor Alpha Enhances Antifungal Activities of Polymorphonuclear and Mononuclear Phagocytes against Aspergillus fumigatus 总被引:4,自引:0,他引:4 下载免费PDF全文
Emmanuel Roilides Anastasia Dimitriadou-Georgiadou Tin Sein Isaac Kadiltsoglou Thomas J. Walsh 《Infection and immunity》1998,66(12):5999-6003
Invasive aspergillosis is a serious complication in immunocompromised patients. The effects of recombinant human tumor necrosis factor alpha (TNF-α) on antifungal activities of human neutrophils (polymorphonuclear leukocytes [PMNs]), human monocytes (MNCs), and rabbit pulmonary alveolar macrophages (PAMs) against Aspergillus fumigatus were studied. The percentage of PMN-induced hyphal damage was increased after 30 min of incubation of PMNs with 0.1 ng of TNF-α per ml at 37°C (P = 0.043). At 0.1 to 10 ng/ml, TNF-α also increased superoxide anion (O2−) produced by PMNs in response to phorbol myristate acetate, N-formylmethionyl leucyl phenylalanine, and unopsonized hyphae (P < 0.01) but did not exert any effect on PMN phagocytosis of conidia in the presence of serum. By comparison, TNF-α induced only a slight increase in O2− production by MNCs in response to phorbol myristate acetate (P = 0.05) and no concomitant increase in the percentage of MNC-induced hyphal damage. Incubation of MNCs with TNF-α at 0.001 to 10 ng/ml for 2 days had no effect on phagocytosis or conidiocidal activity. By contrast, incubation of PAMs with TNF-α at 0.1 to 10 ng/ml for 2 days increased phagocytosis of conidia (P = 0.03). Thus, TNF-α augments the capacity of PMNs to damage Aspergillus hyphae, possibly through enhanced oxidative mechanisms, and increases PAM phagocytic activity against conidia. As such, TNF-α may have an important role in host defense against aspergillosis, and neutralization of its activity may be complicated by increased susceptibility to aspergillosis. 相似文献
42.
Hepatitis C virus (HCV) genotypes in the Caribbean island of Martinique: evidence for a large radiation of HCV-2 and for a recent introduction from Europe of HCV-4 下载免费PDF全文
Martial J Morice Y Abel S Cabié A Rat C Lombard F Edouard A Pierre-Louis S Garsaud P Béra O Chout R Gordien E Deny P Césaire R 《Journal of clinical microbiology》2004,42(2):784-791
Molecular epidemiological studies of hepatitis C virus (HCV) in the Caribbean may help to specify the origin and spread of HCV infection. Indeed, the Caribbean population is intermixed from European and African origins and geographically close to the American continent. We characterized HCV genotypes in the Caribbean island of Martinique. HCV genotypes were analyzed by sequencing or reverse hybridization in the 5' noncoding region (5'NC) in 250 HCV-monoinfected and 85 HCV-human immunodeficiency virus (HIV)-coinfected patients. In addition, sequencing in the nonstructural 5B (NS5B) gene was required to determine the subtype or to perform phylogenetic analysis in selected samples. Genotypes 1 to 6 were found, respectively, in 84.4, 6.8, 5.2, 2.8, 0.4, and 0.4% of 250 HCV-monoinfected patients and in 71.7, 7.1, 15.3, 5.9, 0, and 0% of 85 HCV-HIV-coinfected patients. HCV-1b was found in 66.4% of the HCV-monoinfected patients and was associated with blood transfusion, whereas HCV-1a was detected in 41.2% of the HCV-HIV-coinfected patients and was associated with intravenous drug use (IVDU). The HCV-3 strains belonged to subtype 3a and were linked to IVDU. Phylogenetic analyses were focused on HCV-2 and HCV-4, which are common in Africa. Two opposite patterns were evidenced. NS5B sequences from 19 HCV-2 isolates were affiliated with many different subtypes described either in Europe or in West Africa, suggesting an ancient radiation. In contrast, seven of the nine HCV-4 NS5B sequences ranged within HCV-4a and HCV-4d clusters spreading in continental France by the IVDU route. Epidemiological data demonstrate the recent introduction of HCV-4a and -4d subtypes into the Caribbean. 相似文献
43.
Studies on Acute Methionine Toxicity: I. Nucleolar Disaggregation in Guinea Pig Hepatic Cells with Methionine or Ethionine and Its Reversal with Adenine 下载免费PDF全文
Hisashi Shinozuka Larry W. Estes Emmanuel Farber 《The American journal of pathology》1971,64(2):241-256
The effects of methionine and ethionine on the fine structure of hepatic cell nucleoli of guinea pigs and rats were investigated. A single intraperitoneal injection of methionine into guinea pigs results in the disruption of nucleolonema as early as 2 hours after the injection. By 4 hours, nucleoli show complete fragmentation consisting of many small fragments and small remnants of nucleoli. Large aggregates of interchromatinic granules and condensation of chromatin appear in the nucleoplasm. These changes are remarkably similar to the lesions induced by ethionine in the liver of the rat or the guinea pig. The methionine-induced nuclear and nucleolar lesions persist up to 10 hours after the injection. The administration of adenine 4 hours after the methionine injection reverses the nucleolar lesions by 8 hours. The appearance of incompletely reconstructed nucleoli with twisted ropelike structures suggests a pattern of recovery very similar to the adenine-induced nucleolar reformation in ethionine-treated rats. Injecting methionine into rats induced no nucleolar abnormalities. It is suggested that the mechanism of nucleolar fragmentation induced by methionine or ethionine is related to the accumulation of S-adenosyl compounds with concomitant ATP deficiency in the liver. 相似文献
44.
Tournier JN Hellmann AQ Lesca G Jouan A Drouet E Mathieu J 《Journal of leukocyte biology》2003,73(4):493-501
Fever is one of the most frequent clinical signs encountered in pathology, especially with respect to infectious diseases. It is currently thought that the role of fever on immunity is limited to activation of innate immunity; however, its relevance to activation of adaptive immunity remains unclear. Dendritic cells (DCs) that behave as sentinels of the immune system provide an important bridge between innate and adaptive immunity. To highlight the role of fever on adaptive immunity, we exposed murine bone marrow-derived lipopolysaccharide (LPS)- or live bacteria-maturing DCs over a 3-h period to 37 degrees C or to fever-like thermal conditions (39 degrees C or 40 degrees C). At these three temperatures, we measured the kinetics of cytokine production and the ability of DCs to induce an allogeneic mixed lymphocyte reaction. Our results show that short exposure of DCs to temperatures of 39 degrees C or 40 degrees C differentially increased the secretion of interleukin (IL)-12p70 and decreased the secretion of IL-10 and tumor necrosis factor alpha by maturing DCs. These fever-like conditions induced a regulation of cytokine production at the single-cell level. In addition, short-term exposed LPS-maturing DCs to 39 degrees C induced a stronger reaction with allogeneic CD4(+) T cells than maturing DCs incubated at 37 degrees C. These results provide evidence that temperature regulates cytokine secretion and DC functions, both of which are of particular importance in bacterial diseases. 相似文献
45.
Decreased hypocretin-1 (Orexin-A) levels in the cerebrospinal fluid of patients with myotonic dystrophy and excessive daytime sleepiness 总被引:3,自引:0,他引:3
Martínez-Rodríguez JE Lin L Iranzo A Genis D Martí MJ Santamaria J Mignot E 《Sleep》2003,26(3):287-290
STUDY OBJECTIVE: Myotonic dystrophy type 1 is a multisystem disorder with myotonia, muscle weakness, cataracts, endocrine dysfunction, and intellectual impairment. This disorder is caused by a CTG triplet expansion in the 3' untranslated region of the DMPK gene on 19q13. Myotonic dystrophy type 1 is frequently associated with excessive daytime sleepiness, sharing with narcolepsy a short sleep latency and the presence of sleep-onset rapid eye movement periods during the Multiple Sleep Latency Test. Since narcolepsy is characterized by a dysfunction of the hypothalamic hypocretin system, we investigated whether patients with myotonic dystrophy type 1 with excessive daytime sleepiness have abnormalities in the hypocretin system. DESIGN/PARTICIPANTS: Six patients with myotonic dystrophy type 1 complaining of excessive daytime sleepiness and 13 healthy controls without a sleep disorder were included. The patients with myotonic dystrophy type 1 were evaluated using clinical interviews, nocturnal polysomnograms, and Multiple Sleep Latency Tests. All patients had a confirmed genetic diagnosis for DM1 and were HLA typed. Cerebrospinal fluid hypocretin-1 levels were measured using a direct radioimmunoassay in patients and controls. Setting: University hospital sleep laboratory. INTERVENTIONS: N/A. MEASUREMENT AND RESULTS: The mean sleep latency on Multiple Sleep Latency Tests was abnormal in all patients (< 5 minutes in 2, < or = 8 in 4) and 2 sleep-onset rapid eye movement periods were observed in 2 subjects. All patients were HLA-DQB1*0602 negative. Hypocretin-1 levels were significantly lower in patients versus controls (p < 0.001); 1 case with 2 sleep-onset rapid eye movement periods had hypocretin-1 levels in the range generally observed in narcolepsy (< 110 pg/mL). Three cases had intermediate levels (110-200 pg/mL). Hypocretin-1 levels did not correlate clinically with disease severity or duration or with subjective or objective sleepiness reports. CONCLUSIONS: A dysfunction of the hypothalamic hypocretin system may mediate sleepiness and abnormal Multiple Sleep Latency Test results in patients with myotonic dystrophy type 1. 相似文献
46.
Association of Low Concentrations of Serum Mannose-Binding Protein with Recurrent Infections in Adults 总被引:5,自引:0,他引:5 下载免费PDF全文
Vellalore N. Kakkanaiah Guo Qiu Shen Emmanuel A. Ojo-Amaize James B. Peter 《Clinical and Vaccine Immunology : CVI》1998,5(3):319-321
Low concentrations of mannose-binding protein (MBP; also known as mannose-binding lectin) are associated with common opsonic defect in immunodeficient children. We compared the concentrations of MBP in the sera of 47 adults with non-human immunodeficiency virus-related recurrent infections (group I) and 50 healthy adult controls. Mean serum MBP concentrations in the patient group did not differ significantly from those in the control group (P < 0.4). Nevertheless, the proportion of individuals with less than 5 ng of serum MBP per ml was significantly larger in the patient group (21%, P = 0.01) than in the control group (4%). Group II consisted of 73 pediatric and 56 adult patients with recurrent infections. Pediatric patients had significantly lower mean concentrations of serum MBP than their controls (P < 0.005), and there was no significant difference between the concentrations in sera of adult patients and adult controls (P < 0.4). Again, the proportion of individuals with less than 5 ng of serum MBP per ml was significantly larger in both pediatric (22%, P = 0.045) and adult (38%, P = 0.000016) patients than in their respective controls (4%). Our results demonstrate that, as in children, low concentrations of serum MBP can be associated with recurrent infections in adults. 相似文献
47.
Pooling of sera for human immunodeficiency virus (HIV) testing: an economical method for use in developing countries. 总被引:6,自引:0,他引:6 下载免费PDF全文
To determine whether donated blood samples in African countries could be pooled, then tested for the presence of human immunodeficiency virus (HIV) antibodies with a single test without loss of accuracy, a single test on five pooled samples was used, followed by individual testing of positive pools. This resulted in no loss of either sensitivity or specificity. Pooling 10 samples resulted in a loss of sensitivity for low antibody titre specimens. Pooling reduced the costs of screening by 70% and time needed for analysis. It is concluded that pooling of five samples for HIV screening may result in a substantial reduction in costs; in countries where the prevalence of HIV is higher than the 2-3% found in Zimbabwean donors, however, savings may not be as great. 相似文献
48.
Human phagocytic cell responses to Scedosporium apiospermum (Pseudallescheria boydii): variable susceptibility to oxidative injury 下载免费PDF全文
Gil-Lamaignere C Roilides E Lyman CA Simitsopoulou M Stergiopoulou T Maloukou A Walsh TJ 《Infection and immunity》2003,71(11):6472-6478
Scedosporium apiospermum (Pseudallescheria boydii) is an emerging opportunistic filamentous fungus that causes serious infections in both immunocompetent and immunocompromised patients. To gain insight into the immunopathogenesis of infections due to S. apiospermum, the antifungal activities of human polymorphonuclear leukocytes (PMNs), mononuclear leukocytes (MNCs), and monocyte-derived macrophages (MDMs) against two clinical isolates of S. apiospermum were evaluated. Isolate SA54A was amphotericin B resistant and was the cause of a fatal disseminated infection. Isolate SA1216 (cultured from a successfully treated localized subcutaneous infection) was susceptible to amphotericin B. MDMs exhibited similar phagocytic activities against conidia of both isolates. However, PMNs and MNCs responded differently to the hyphae of these two isolates. Serum opsonization of hyphae resulted in a higher level of superoxide anion (O(2)(-)) release by PMNs in response to SA54A (amphotericin B resistant) than that seen in response to SA1216 (amphotericin B susceptible; P < 0.001). Despite this increased O(2)(-) production, PMNs and MNCs induced less hyphal damage to SA54A than to SA1216 (P < 0.001). To investigate the potential mechanisms responsible for these differences, hyphal damage was evaluated in the presence of antifungal oxidative metabolites as well as in the presence of a series of inhibitors and scavengers of antifungal PMN function. Mannose, catalase, superoxide dismutase, dimethyl sulfoxide, and heparin had no effect on PMN-induced hyphal damage to either of the two isolates. However, azide, which inhibits PMN myeloperoxidase activity, significantly reduced hyphal damage to SA1216 (P < 0.01) but not to SA54A. Hyphae of SA1216 were slightly more susceptible to oxidative pathway products, particularly HOCl, than those of SA54A. Thus, S. apiospermum is susceptible to antifungal phagocytic function to various degrees. The selective inhibitory pattern of azide with respect to hyphal damage and the parallel susceptibility to HOCl suggests an important difference in susceptibilities to myeloperoxidase products that may be related to the various levels of pathogenicity and amphotericin B resistance of S. apiospermum. 相似文献
49.
Donnadieu E Jouvin MH Rana S Moffatt MF Mockford EH Cookson WO Kinet JP 《Immunity》2003,18(5):665-674
Allergic reactions are triggered via crosslinking of the high-affinity receptor for immunoglobulin E, F(c)epsilonRI. In humans, F(c)epsilonRI is expressed as a tetramer (alphabetagamma(2)) and a trimer (alphagamma(2)). The beta subunit is an amplifier of F(c)epsilonRI surface expression and signaling. Here, we show that as a consequence of alternative splicing, the F(c)epsilonRIbeta gene encodes two proteins with opposing and competing functions. One isoform is the full-length classical beta, the other a novel truncated form, beta(T). In contrast to beta, beta(T) prevents F(c)epsilonRI surface expression by inhibiting alpha chain maturation. Moreover, beta(T) competes with beta to control F(c)epsilonRI surface expression in vitro. We propose that the relative abundance of the products of the beta gene may control the level of F(c)epsilonRI surface expression and thereby influence susceptibility to allergic diseases. 相似文献
50.
Petros M Pavlopoulos Anastasia E Konstantinidou Emmanuel Agapitos Panagiotis Davaris 《Clinical genetics》1998,54(6):512-516
Roberts syndrome (RS) is a rare autosomal recessive disorder characterized primarily by symmetric reduction anomalies of all limbs, growth retardation and craniofacial abnormalities. Most RS patients are reported to present a typical abnormality of their constitutive heterochromatin, accompanied by abnormal cytological growth characteristics. We present an extremely severe case of an RS fetus, karyotypically documented, with a clinical presentation including growth deficiency, tetraphocomelia, frontal meningocele, craniofacial abnormalities and penile enlargement with hypospadias. Nuclear morphometrical analysis in tissues of various organs revealed a reduced nuclear size in RS as compared to normal controls, and statistically significant differences in morphometric parameters related to the nuclear shape. Immunohistochemical study of the same organs showed a reduced expression of proliferating cell nuclear antigen in the presented case, thus indicating a decreased cell proliferation rate in RS. Our results reconfirm previously reported findings in cultured fibroblasts of RS cases, thereby reinforcing on a histologic level, the hypothesis that reduced cell proliferation may be involved in the growth retardation and the reduction abnormalities observed in RS. 相似文献